The influence of solvent and sequence on peptide conformation is being investigated with the purpose of developing a predictive understanding which may be useful in rational design of peptides for their biological activity. Data on conformational distributions and equilibria of selected synthetic peptides in various solvents, including especially water, are being obtained by nuclear magnetic resonance and circular dichroism spectroscopy. Conformational equilibrium data from cyclic hexapeptides are being interpreted to identify solvent and side chain effects. Crystallographic studies of some of the same peptides are being made in a search for modes of water-peptide interactions. Most of the peptides used are synthesized as part of this program. Additional cyclic peptides are being synthesized to establish new classes of conformationally stable peptide rings. Effects of solvation are being modelled in conformational energy calculations to match the solution data. A study of chain folding in LHRH and analogs is proceeding.